PT  - JOURNAL ARTICLE
AU  - Gualdani, Roberta
AU  - Yuan, Jun-Hui
AU  - Effraim, Philip R.
AU  - Di Stefano, Giulia
AU  - Truini, Andrea
AU  - Cruccu, Giorgio
AU  - Dib-Hajj, Sulayman D.
AU  - Gailly, Philippe
AU  - Waxman, Stephen G.
TI  - Trigeminal Neuralgia TRPM8 Mutation
AID  - 10.1212/NXG.0000000000000550
DP  - 2021 Feb 16
TA  - Neurology Genetics
PG  - e550
VI  - 7
IP  - 1
4099  - http://ng.neurology.org/content/7/1/e550.short
4100  - http://ng.neurology.org/content/7/1/e550.full
SO  - Neurol Genet2021 Feb 16; 7
AB  - Objective To assess the functional effects of a variant, c.89 G > A (p.Arg30Gln), in the transient receptor potential melastatin 8 (TRPM8) cold-sensing, nonselective cation channel, which we have previously identified in a patient with familial trigeminal neuralgia.Methods We carried out Ca2+ imaging and whole-cell patch-clamp recording.Results The TRPM8 mutation enhances channel activation, increases basal current amplitude and intracellular [Ca2+] in cells carrying the mutant channel, and enhances the response to menthol.Conclusions We propose that Arg30Gln confers gain-of-function attributes on TRPM8, which contribute to pathogenesis of trigeminal neuralgia in patients carrying this mutation.DMEM=Dulbecco's Modified Eagle's Medium; EGTA=ethylene glycol tetraacetic acid; FBS=fetal bovine serum; GFP=green fluorescent protein; HEPES=4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; HEK=human embryonic kidney; TN=trigeminal neuralgia; TRPM8=transient Receptor Potential Melastatin 8